RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Circulating Hsp70 Levels and the Immunophenotype of Peripheral Blood Lymphocytes as Potential Biomarkers for Advanced Lung Cancer and Therapy Failure after Surgery.
Circulating Hsp70 Levels and the Immunophenotype of Peripheral Blood Lymphocytes as Potential Biomarkers for Advanced Lung Cancer and Therapy Failure after Surgery.
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肺癌仍是一种预后较差的严重疾病。若能建立生物标志物特征组合,用于区分原发性肺癌与肺转移并检测治疗失败,将显著改善患者管理,并有助于制定个体化、风险适配的治疗决策。
本研究采用ELISA测量循环Hsp70水平,并通过多参数流式细胞术分析外周血淋巴细胞免疫表型,旨在为肺癌术前和术后患者、肺转移患者以及患有炎症性肺病慢性阻塞性肺疾病(COPD)的患者寻找预测性生物标志物特征。健康对照的Hsp70浓度最低,其次为晚期COPD患者;随着肿瘤分期进展和出现转移,Hsp70水平逐步升高。早期复发患者术后3个月内Hsp70水平开始上升,而无复发患者未见明显变化。早期复发还与B细胞显著减少、调节性T细胞增加相关;无复发患者则T细胞和NK细胞水平升高。研究认为,循环Hsp70浓度可能有助于区分肺癌与转移性疾病,并预测肺癌患者肿瘤晚期和早期复发。仍需在更大患者队列和更长随访中验证Hsp70及免疫表型能否作为预测性生物标志物特征。
Lung cancer remains a devastating disease with a poor clinical outcome. A biomarker signature which could distinguish lung cancer from metastatic disease and detect therapeutic failure would significantly improve patient management and allow for individualized, risk-adjusted therapeutic decisions. In this study, circulating Hsp70 levels were measured using ELISA, and the immunophenotype of the peripheral blood lymphocytes were measured using multiparameter flow cytometry, to identify a predictive biomarker signature for lung cancer patients pre- and post-operatively, in patients with lung metastases and in patients with COPD as an inflammatory lung disease.
The lowest Hsp70 concentrations were found in the healthy controls followed by the patients with advanced COPD. Hsp70 levels sequentially increased with an advancing tumor stage and metastatic disease. In the early-recurrence patients, Hsp70 levels started to increase within the first three months after surgery, but remained unaltered in the recurrence-free patients. An early recurrence was associated with a significant drop in B cells and an increase in Tregs, whereas the recurrence-free patients had elevated T and NK cell levels.
We conclude that circulating Hsp70 concentrations might have the potential to distinguish lung cancer from metastatic disease, and might be able to predict an advanced tumor stage and early recurrence in lung cancer patients.
Further studies with larger patient cohorts and longer follow-up periods are needed to validate Hsp70 and immunophenotypic profiles as predictive biomarker signatures.
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